Joo-Hee Yoon

HCCR-1, a novel oncogene, encodes a mitochondrial outer membrane protein and suppresses the UVC-induced apoptosis.

BackgroundThe Human cervical cancer oncogene (HCCR-1) has been isolated as a human oncoprotein, and has shown strong tumorigenic features. Its potential role in tumorigenesis may result from a negative regulation of the p53 tumor suppressor gene.ResultsTo investigate the biological function of HCCR-1 in the cell, we predicted biological features using bioinformatic tools, and have identified a LETM1 homologous domain at position 75 to 346 of HCCR-1. This domain contains proteins identified from diverse species predicted to be mitochondrial proteins. Fluorescence microscopy and fractionation experiments showed that HCCR-1 is located in mitochondria in the COS-7, MCF-7 and HEK/293 cell lines, and subcompartamentally at the outer membrane in the HEK/293 cell line. The topological structure was revealed as the NH2-terminus of HCCR-1 oriented toward the cytoplasm. We also observed that the D1-2 region, at position 1 to 110 of HCCR-1, was required and sufficient for posttranslational mitochondrial import. The function of HCCR-1 on mitochondrial membrane is to retard the intrinsic apoptosis induced by UVC and staurosporine, respectively.ConclusionOur experiments show the biological features of HCCR-1 in the cell, and suggest that uncontrolled expression of HCCR-1 may cause mitochondrial dysfunction that can result in resisting the UVC or staurosporine-induced apoptosis and progressing in the tumor formation.

Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p < 0.05), but was not significantly different between HPV16 single and multiple-type HPV infections (p > 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (≥CIN3) in HPV L1-positive cases.

Apoptosis-related mRNA expression profiles of ovarian cancer cell lines following cisplatin treatment

OBJECTIVE The aim of this study was to identify apoptosis-related genes of ovarian cancer cell lines following cisplatin treatment. METHODS We used IC(50) values and fluorescence-activated cell sorting analysis to compare cell death in 2 ovarian cancer cell lines, namely, SKOV-3 and OVCAR-3, upon treatment with cisplatin. Moreover, the change in transcriptional levels of apoptosis-associated genes was measured with a dendron-modified DNA microarray. RESULTS The protein levels for the up-regulated genes in each cell line were validated to identify the molecules that may determine the cellular behavior of cisplatin resistance. Eight genes were over-expressed in the 2 cell lines. The cisplatin-induced up-regulation of DAD1 in transcriptional and protein levels contributed to the cisplatin resistance of OVCAR-3, and the up-regulation of FASTK and TNFRSF11A in SKOV-3 resulted in its higher sensitivity to cisplatin than that of OVCAR-3. CONCLUSION In the present study, we have identified a set of genes responsible for apoptosis following cisplatin treatment in ovarian cancer cell lines. These genes may give information about the understanding of cisplatin-induced apoptosis in ovarian cancer.

Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy

Purpose To evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy. Materials and Methods The records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy. Results Twenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications. Conclusion Outcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

Correlation between the Digital Cervicography and Pathological Diagnosis Performed at Private Clinics in Korea

Objective: To evaluate the correlation tendency between abnormal findings of digital cervicography and cervical pathology at private clinics in Korea. Methods: Abnormal finding of digital cervicography performed at private clinics in Korea between January 1, 2010 and May 31, 2012 were analysed retrospectively. The patients age, abnormal findings of digital cervicography, cervical cytology, human papillomaviru (HPV) test and cervical pathology were investigated and the rate of agreement between abnormal finding of digital cervicography and cervical pathology results was calculated. Abnormal findings of digital cervicography were divided into 4 categories: atypical, compatible with CIN1, compatible with CIN2/3 and compatible with cancer. Results: The study group was composed of 1547 women with a mean (range) age of 37.4 (14-91 years). The agreement rate between abnormal findings of digital cervicography and cervical pathology was 52.0% in “compatible with CIN1”, 78.9% in “compatible with CIN2/3”, and 90.2% in “compatible with cancer”. Conclusions: Abnormal findings of digital cervicography were highly concordant with cervical intraepithelial neoplasia (CIN) and cancer examined at outpatient clinics in Korea. Therefore, abnormal interpretations of digital cervicography can be used as an excellent auxiliary technique with cervical cytology for CIN and cancer.

Neoadjuvant Chemotherapy for Cervical Cancer: Rationale and Evolving Data

Cervical cancer is still the second most common female malignancy and the second most common cause of cancer-related mortality in women worldwide. [1] In 1999, the National Cancer Institute showed that in addition to radiotherapy, cisplatin chemotherapy produced a therapeutic effect in women with locally advanced cervical cancer (LACC) in 5 randomized trials. [2-7] However, the standard treatments for early cervical cancer have traditionally comprised radical hysterectomy with lymph node dissection or cisplatin-based chemoradia‐ tion. [8] Unfortunately, poor prognosis was observed in patients with tumors more than 4 cm in diameter and a poor survival rate of 50–60% was noted in patients with large tumors. To improve the therapeutic results, a new approach with neoadjuvant chemotherapy (NACT) followed by radical surgery or chemoradiation has been introduced. The definition of NACT in cervical cancer is the administration of chemotherapy for the purpose of reducing the cancer volume before the main treatment. In the late 1980s, a pilot study of NACT with cisplatin, bleomycin, and methotrexate performed for 33 patients with a tumor larger than 4 cm showed a response rate of 75.7% (complete response 12.1%, partial response 63.6%) on histologic examination. The sites showing a sensitive response to NACT were the vagina, cervix, and parametrium, in that order. [9] In 1989, Kim et al. performed NACT with vinblastine, bleo‐ mycin, and cisplatin (VBP) in 54 patients and reported a high response rate (81.0%), a low incidence of lymph node metastasis (20%), and an improvement in the 2-year tumor free survival rate (94%). [10]

A laparoscopic sacrohysteropexy to manage uterine prolapse after surgical failure via a vaginal approach.

Case report A 22-year-old woman G2P2 presented to the emergency department with intra-abdominal bleeding following blunt abdominal trauma. Splenectomy was done because of bleeding from splenic lacerations and two prophylactic silicone peritoneal drains were placed: one in the left subdiaphragmatic space and the other in the pouch of Douglas. Following the removal of the left subdiaphragmatic drain on the third postoperative day, she developed abdominal pain and tenderness. At repeat laparotomy, the bleeding sites at the splenectomy location were controlled. Additionally, the right fallopian tube was noticed to be suctioned into the drain passing through one side hole and exiting through the opposite one (Figure 1). Th e drain was incised and the tube was released without apparent injury.